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A putative exonic splicing enhancer in exon 7 of the PDHA1 gene affects splicing of adjacent exons.
[pyruvate dehydrogenase deficiency]
A
nonsense
mutation
(
c
.
729
C
>
A
,
Y
243
X
)
in
exon
7
of
the
PDHA
1
gene
in
a
patient
with
pyruvate
dehydrogenase
deficiency
results
in
aberrant
splicing
of
the
primary
transcript
with
production
of
stable
mRNAs
which
lack
either
both
exons
6
and
7
or
exon
7
alone
.
Transfection
and
expression
of
genomic
constructs
covering
exons
5
to
8
of
the
mutant
PDHA
1
gene
reproduced
this
aberrant
splicing
in
vitro
.
The
same
pattern
of
abnormal
splicing
was
found
when
a
silent
mutation
was
introduced
at
the
same
position
.
Both
the
nonsense
and
silent
mutations
alter
a
strong
consensus
site
for
the
binding
of
SRp
40
,
suggesting
that
they
may
interfere
with
an
exonic
splicing
enhancer
in
exon
7
of
the
gene
.
However
,
this
appears
to
affect
splicing
of
not
only
exon
7
,
but
also
the
adjacent
upstream
exon
.
The
splice
acceptor
site
of
intron
5
has
weak
homology
to
the
consensus
sequence
and
this
may
contribute
to
the
combined
splicing
defect
.
